title: Associations of ABCB1 and XPC genetic polymorphisms with susceptibility to colorectal cancer and therapeutic prognosis in a Chinese population.
abstract: Associations between ABCB1 and XPC genetic polymorphisms and risk of developing colorectal cancer (CRC) as well as clinical outcomes in CRCs with chemotherapy were investigated. A case-control study was performed on the ABCB1 C3435T, G2677T/A and XPC Lys939Gln polymorphisms in 428 CRC cases and 450 hospital- based, age and sex frequency-matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. We observed that the ABCB1 3435CT or CC+CT variants were significantly linked with increasing risk of developing CRC (adjusted OR (95% CI): 1.814 (1.237-2.660), P=0.0022; adjusted OR (95% CI): 1.605 (1.117-2.306), P=0.0102, respectively). Moreover, the distribution frequency of XPC AC genotype or AC+CC genotypes also showed a tendency towards increasing the suscepbility for CRC (P=0.0759 and P=0.0903, respectively). Kaplan-Meier curves showed that the ABCB1 C3435T variant was associated with a tendency toward longer progression-free survival (PFS) (n=343, Log-rank test: P=0.063), and the G2677T/A variant genotypes (GT+TT+GA+AA) with a tendency for longer OS in postoperative oxaliplatin-based patients (n=343, Log-rank test: P=0.082). However, no correlation of the XPC Lys939Gln polymorphism was found with PFS and OS in patients with postoperative oxaliplatin-based chemotherapy (n=343). Our study indicated that ABCB1 polymorphisms might be candidate pharmacogenomic factors for the prediction of CRC susceptibility, but not for prognosis with oxaliplatin chemosensitivity in CRC patients.
authors.affiliation: Oncological Surgery Department of Xinxiang Central Hospital, Xinxiang, Henan, China. aiminyue@163.com
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Yue
authors.forename: Zhen-Bin
authors.initials: ZB
authors.lastname: Xie
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Zhao
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Guo
authors.forename: Yu-Hou
authors.initials: YH
authors.lastname: Shen
authors.forename: Hai-Pu
authors.initials: HP
authors.lastname: Wang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C086984:XPC protein, human